Help Section | Introduction | Extracellular and Binding | Gate

This page was created by: Chris Downing and Maureen Handoko

Article Information

Miyazawa, Atsuo; Fujiyoshi, Yoshinori; Unwin, Nigel.
Structure and Gating Mechanism of the Acetylcholine Receptor Pore.
Nature 423, 949 - 955 (26 June 2003)

Help Section

Use the push button on the left to select a pdb model to load from the model category. Then select other push buttons under the options category to look at different views of the selected model. You can select a new model to load at any time. While reading the following sections, make sure to select models and look at the different variables in the options section.

Introduction

Acetylcholine receptor pore is a member of the transmitter-gated ion pores, and can be found spanning the postsynaptic membranes at the nerve to muscle synapse. This pore allows ion flow into the cell as acetylcholine enters the ligand-binding domain of the receptor, which then initiates an action potential. There are two main functional portions of the receptor protein, one is extracellular and the other is embedded in the membrane. There are five subunits of the membrane portion of the protein, which are termed A, B, C, D, and E. Subunit D is an identical repeat of A, and they both provide the connection between the membrane-spanning and the extracellular portion of the protein. Each of the five subunits has four alpha-helices that span the membrane, three of which are (membrane) lipid-facing while the fourth is pore-facing. The five pore-facing helices from each subunit make up the actual pore, and are responsible for the gating function of the protein.

Extracellular Ligand Binding Domain

As described in the introduction there are extracellular portions of the protein that consist mostly of beta sheets and are not included in this chime modeling page. These extracellular parts, often only labeled as the alpha strands, are connected to the A and D repeat units of the membrane-spanning portion of the protein. Each of the alpha strands binds acetylcholine, the neurotransmitter, and causes a conformation change which is then transmitted to the inner five helices. This change in conformation results in the opening of the pore through the rotation of the inner (pore-facing) helices within the membrane portion of the protein.

Gate

The pore is cation selective and only allows hydrated sodium or potassium ions to pass through. The middle of the pore is constricted due to the small separation of the helices and to the presence of bulky hydrophobic side chains. The most kinked part of the passage represents the gate. The inner helices are closely identical, and the equivalent surfaces of the homologous residues from each helix form ‘levels’ through the entire passage. The gate is made up of identical interactions between residues of the five helices, the main ones being hydrophobic interactions between phenylalanine and valine or isoleucine, and that of leucine with alanine or serine. These interactions create a tight hydrophobic girdle around the pore, which presents a barrier to the flow of hydrated ions across the membrane. Hydrated ions are not able to pass this gate, unless the conformational change has taken place, in which the inner helices were rotated and the hydrophobic interactions between the residues that make up the gate were disrupted.

Be sure to select the five inner helices model, select charged atoms, then hydrophobic atoms, and lastly the gate atoms.